rs2278741

chr2-120991491-G-Cchr2-120991491-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001374353.1(GLI2):c.*816G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 152,546 control chromosomes in the GnomAD database, including 29,689 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.61 (29568 hom., cov: 32)
  • Exomes 𝑓: 0.70 (121 hom.)
• Consequence: GLI2 NM_001374353.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.257

Genes affected

GLI2 (HGNC:4318): (GLI family zinc finger 2) This gene encodes a protein which belongs to the C2H2-type zinc finger protein subclass of the Gli family. Members of this subclass are characterized as transcription factors which bind DNA through zinc finger motifs. These motifs contain conserved H-C links. Gli family zinc finger proteins are mediators of Sonic hedgehog (Shh) signaling and they are implicated as potent oncogenes in the embryonal carcinoma cell. The protein encoded by this gene localizes to the cytoplasm and activates patched Drosophila homolog (PTCH) gene expression. It is also thought to play a role during embryogenesis. The encoded protein is associated with several phenotypes- Greig cephalopolysyndactyly syndrome, Pallister-Hall syndrome, preaxial polydactyly type IV, postaxial polydactyly types A1 and B. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 2-120991491-G-C is Benign according to our data. Variant chr2-120991491-G-C is described in ClinVar as [Benign]. Clinvar id is 331006.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLI2	NM_001374353.1	c.*816G>C		3_prime_UTR_variant	14/14	ENST00000361492.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLI2	ENST00000361492.9	c.*816G>C		3_prime_UTR_variant	14/14	1	NM_001374353.1	P2

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92169 AN: 151956 Hom.: 29559 Cov.: 32

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.803

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.730

Gnomad OTH AF: 0.634

GnomAD4 exome AF: 0.697 AC: 329 AN: 472 Hom.: 121 Cov.: 0 AF XY: 0.702 AC XY: 205 AN XY: 292

Gnomad4 ASJ exome AF: 1.00

Gnomad4 FIN exome AF: 0.701

Gnomad4 NFE exome AF: 0.658

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.606 AC: 92185 AN: 152074 Hom.: 29568 Cov.: 32 AF XY: 0.602 AC XY: 44748 AN XY: 74316

Gnomad4 AFR AF: 0.397

Gnomad4 AMR AF: 0.627

Gnomad4 ASJ AF: 0.673

Gnomad4 EAS AF: 0.476

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.661

Gnomad4 NFE AF: 0.730

Gnomad4 OTH AF: 0.636

Alfa AF: 0.551 Hom.: 1731

Bravo AF: 0.592

Asia WGS AF: 0.492 AC: 1709 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Holoprosencephaly 9 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	7.2
Dann	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2278741; hg19: chr2-121749067; COSMIC: COSV58040492; COSMIC: COSV58040492;